(1) Field of the Invention
This invention relates to pharmaceuticals suitable for use in the treatment of peptic ulcer disease. Peptic ulcer is an ulceration of the mucous membrane of the stomach and/or duodenum; the mucous membrane is damaged by the action of hydrochloric acid and pepsin due to its decreased resistance to the aggressive factors induced by various causes including physical and psychological stress.
(2) Problems to Be Solved by the Invention
Until recently, sodium bicarbonate and aluminum compounds had been used to neutralize gastric acid as aggressive factor. The drugs commonly used now to treat peptic ulcer disease include anticholinergics, gastroprotective agents, drugs improving mucosal blood flow, and H.sub.2 -receptor antagonists.
Drugs for peptic ulcers are administered for a long period of time and are required to have the fewest adverse effects as well as high efficiency. However, the available drugs are not necessarily satisfactory in safety and efficacy. In addition there is another problem associated with the use of the drug, namely, the relapse of ulcer after drug treatment is stopped. For example, the H.sub.2 -receptor antagonists are very effective in improving gastric and duodenal ulcers by inhibiting gastric acid secretion but ulcers recur at high incidence after discontinuing treatment with the drugs.
On the other hand, pentoxifylline, the compound of the general formula I where in R.sup.1 is 5-oxohexyl and R.sup.2 and R.sup.3 are methyl has already been reported by Vorobyev and Samsonov to have antiulcer effects (Ter. Arkh. 57, 52-55, 1985). Moreover, it has been described in Japanese Laid-Open Patent Publication 225317/88 that the compounds represented by the general formula I wherein R.sup.1 is 4-oxopentyl or 5-oxohexyl, R.sup.2 is methyl or ethyl and R.sup.3 is C.sub.2 -C.sub.4 alkyl have antiulcer effect superior to that of pentoxifylline.
As a result of our extensive studies for superior therapeutics for peptic ulcer disease, we have found that specific xanthine derivatives have high efficiency and safety enough to be new drugs suitable for use in the treatment of the disease, inclusive of irritations of the gastro-intestinal mucosa caused by drugs such as non-steroidal anti-inflammatory agents.